DNA immunization of male mice towards proacrosin and impaired fertility

GARCÍA, L.; VEAUTE, C.; LUSTIG, L.; VAZQUEZ LEVIN, M.H.

Catalonia Palace of Congress. Barcelona, España.

Congreso; 9th International Congress of Andrology; 2009

International Society of Androlgy

Immunity to sperm antigens has been associated with impaired fertility, both in humans and in animal models. Previous work of our group demonstrated that DNA immunization of female mice with human proacrosin (h-proacrosin) was associated to diminished fertilization. The present study evaluated the effect of proacrosin DNA immunization of male mice upon fertility. The cDNA of h-proacrosin was subcloned in an eukaryotic expression vector, under CMV transcription control (pSF2-Acro). Male Balb/c mice were inoculated i.m. 5 times with 50µg of plasmid, three weeks apart; control animals were inoculated with plasmid without insert. Humoral response was evaluated by an indirect ELISA with recombinant h-proacrosin as antigen. At week 15, mice were mated with females of proven fertility. Once mated, males were sacrificed and analyzed. Animals receiving pSF2-Acro showed high levels of anti-proacrosin antibodies. All mice with anti-proacrosin antibodies levels higher than 4 times the preimmune value were infertile. Histological analysis of the testis did not show alterations in pSF2-Acro injected animals. No differences were observed between treated and control animals when comparing sperm number, motility or A23187 calcium ionophore-induced acrosome reaction. Nevertheless, the acrosome reaction in control spermatozoa in the presence of sera from immunized animals was inhibited (% of reacted sperm at 60 min: 18±2 vs 75±1.5; p<0.05). Conclusion: DNA immunization of male mice towards proacrosin induced a specific humoral response that was associated to a reduced fertility. Evidence from this study related the impaired fertility to a diminished acrosome reaction. Proacrosin could be considered as a candidate for immunocontraception.